not contain this structural function or have structures where it is sterically
hindered. If, for example, the drug is rapidly metabolized by esterases in the
plasma, compounds that are more stable to these enzymes would be tested.
Alternatively, the drug may be poorly absorbed because it is very water soluble,
in which case the approach is to produce and test less water soluble analogues.
Pharmacokinetics may be used to provide the information required to design
dosage regimens (section 2.6). It has been particularly useful in determining drug
dosages for patients with damaged organs. It is also used to obtain information
concerning the effect of drug metabolites in humans and other mammals.
8.3 Pharmacokinetic models
The accurate assessment of the results of a pharmacokinetic investigation re-
quires the use of mathematical methods. In order to apply these methods to the
behaviour of a drug, in what is a complex biological system it is necessary to use
so calledmodelsystems. The commonly usedcompartmental modelvisualizes a
biological system as a series of interconnected compartments (Figure 8.3). It
allows the biological relationships between these compartments to be expressed
in the form of mathematical equations. In all compartmental models, a com-
partment is defined as a group of tissues that have a similar blood flow and drug
affinity. It is not necessarily a defined anatomical region in the body; however,
all compartmental models systems assume that:
1. the compartments communicate with each other by reversible processes,
2. rate constants are used as a measure of the rate of entry and exit of a drug
from a compartment,
3. the distribution of a drug within a compartment is rapid and homogeneous
and
4. each drug molecule has an equal chance of leaving a compartment.
Compartmental models are normally based on a central compartment, which
represents the plasma and the highly perfused tissues (Figure 8.3). Elimination
(see section 2.7.1) of a drug is assumed to occur only from this compartment since
the processes associated with elimination occur mainly in the plasma and the
highly perfused tissues of the liver and kidney. Other compartments are con-
nected to the central compartment as required by the nature of the investigation.
PHARMACOKINETIC MODELS 161